The quality of life of patients with hypoventilation and home mechanical ventilation (HMV) has not been well described. Modern quality of life assessment techniques were therefore introduced in a cross-sectional study of patients treated with HMV. The aim was to study various aspects of the patient's quality of life and relate them to the underlying diseases, blood gases and the type of ventilatory connection. The study comprised 39 patients, most of them ventilated only during the night (n = 35). Nasal ventilation predominated (n = 29). Patients treated with HMV reported satisfactory levels of both psychosocial functioning and mental well-being that compared well with a general population group. Their quality of sleep was generally good. The quality of life measures were mainly influenced by the patients' underlying disease. Patients with scoliosis expressed in almost all instances the best quality of life. The quality of life of patients with ventilation by tracheostomy was reported to be at least as good as that of patients with nasal ventilation. The global quality of life estimation was mainly determined by the mental state of the patients and their sleep quality and only to a minor extent by physical handicaps. In conclusion, the patients treated with HMV reported good psychosocial functioning and mental well-being, in spite of severe physical limitations and dependence on regular nocturnal ventilation.